Physiology and Pathophysiology
Lung Physiology.
The terminal airspaces of the lungs, the alveoli, are lined with a thin liquid lining layer. Thus there is an air-liquid interface in the lungs that has an associated surface tension. Alveolar type II epithelial cells release lung surfactant—an aggregate of phospholipids and proteins—into the liquid lining layer. The surfactant adsorbs to and reduces surface tension at the air-liquid interface. By lowering surface tension, surfactant reduces the pressure required to keep the lungs inflated and reduces the work of breathing.
ARDS.
The acute respiratory distress syndrome (ARDS), can result from a variety of initial insults. ARDS has an incidence of about 200,000 cases per year in the United States, with a mortality rate exceeding 35%. For the purpose of the present disclosure, ARDS includes acute lung injury (ALI), which has been reclassified as mild ARDS.
In ARDS, inflammation is present in the lungs. With inflammation, pulmonary vascular permeability increases and liquid leaks out of the blood vessels into the surrounding interstitial tissue. The liquid carries plasma proteins with it. When enough liquid escapes from the vessels, liquid begins to enter the alveoli, a condition known as alveolar edema. Initially, discrete alveoli in the dependent (bottom portion of the) lung become flooded and are interspersed with alveoli that remain aerated. With disease progression, most alveoli in the dependent lung become flooded; in the nondependent lung, some alveoli become flooded and are interspersed with other alveoli that remain aerated. From the onset of edema, the additional liquid in the interstitium and airspace effectively thickens the alveolar-capillary membrane across which oxygen and carbon dioxide must pass, making gas exchange difficult. Further, in ARDS, lung compliance is reduced, which makes breathing difficult.
ARDS patients are treated by mechanical ventilation, which assists gas exchange and keeps patients alive but often causes an over-distension injury (ventilator-induced lung injury, VILI) that exacerbates the underlying lung disease and prevents patient recovery. It is now standard protocol to ventilate with a low tidal (breath) volume that has been shown to decrease mortality. However, mortality still exceeds 35%.
It has been hoped that administration of exogenous surfactant would reduce surface tension, increase lung compliance and protect against VILI. Thus, multiple randomized clinical trials have tested tracheal administration of exogenous surfactant in ARDS patients. However, exogenous surfactant administration has not reduced mortality, excepting in one pediatric study.
In VILI, the site of over-distension injury is likely in aerated alveoli adjacent to flooded alveoli. In flooded alveoli, the air-liquid interface forms a concave meniscus. Due to surface tension at the meniscus and pressure drop across the meniscus, flooded alveoli are shrunken and adjacent aerated alveoli are, due to interdependence, expanded. Mechanical ventilation significantly exacerbates the over-expansion of aerated alveoli located adjacent to flooded alveoli.
Neonatal Respiratory Distress Syndrome (RDS).
Surfactant production increases markedly during the third trimester of gestation. Premature babies born prior to or early in the third trimester used not to survive. Since the 1980's, tracheal instillation of exogenous surfactant has enabled such premature babies to live. However, there remains room for improvement in the clinical treatment of neonatal RDS.
High Frequency Modes of Lung Treatment.
For various objectives such as loosening/clearance of airway mucus and improved mechanical ventilation, the lung has sometimes been subjected to percussion or to high frequency ventilation. Devices designed to implement such treatments, and the frequencies at which they operate, include: pneumatically and electrically powered percussors; intrapulmonary percussive ventilation (1.7-5 Hz); flutter valve therapy; high-frequency chest wall oscillation (5-25 Hz); high frequency positive-pressure ventilation (1-1.8 Hz); high-frequency jet ventilation (up to 10 Hz); high-frequency oscillatory ventilation (1-50 Hz); high-frequency flow interruption (up to 15 Hz, where the flow interruption occurs during inspiration, not expiration); and high-frequency percussive ventilation (up to 2 Hz). None of these ‘high-frequency’ treatments operate at a frequency greater than 50 Hz.
Active Deflation.
Certain existing modes of mechanical ventilation have incorporated active deflation. Although now out of use, ventilation with negative end-expiratory pressure (NEEP)—available on Puritan Bennett AP series and Bird Mark 7 and 8 ventilators—can use a Venturi tube to actively draw air out of the airways and lower the minimal tracheal entrance pressure at end-expiration below atmospheric pressure. In a Venturi tube, a high pressure gas jet is forced through a small orifice at the tube end while a different gas enters through a second port at lower velocity. The jet accelerates the lower velocity gas by entrainment.
High-frequency oscillatory ventilation uses an oscillator to move a diaphragm at one end of a chamber that is incorporated into the mechanical ventilation circuit proximal to the endotracheal tube. On its forward stroke the oscillator compresses air within the chamber; on its backward stroke it expands air within the chamber. During the backward stroke, tracheal pressure may become negative. HFOV is most frequently used in neonatal ventilation, although it is used in adults as well.